Device and method for examining a body lumen

ABSTRACT

An in vivo examining device and method are described. The in vivo examining device has two operational phases; an initial phase in which the device is of initial dimensions and a final phase in which the device is of final dimensions. In the initial phase the device can pass freely through a normally configured body lumen whereas it may not be able to pass freely through an abnormally configured lumen. In the final phase the device can pass freely through a body lumen even if it is abnormally configured.

FIELD OF THE INVENTION

[0001] The present invention relates to a device and method forexamining a body lumen. The device and method are useful, inter alia, indetecting abnormalities in a body lumen configuration.

BACKGROUND OF THE INVENTION

[0002] Tubular organs in the body may have a convoluted cavityconfiguration. The gastrointestinal tract, for example, starts from theoral cavity and proceeds through the esophagus, stomach, duodenum andsmall intestine, which is a long tube that folds many times to fitinside the abdomen. The small intestine is connected to the largeintestine, which begins with the cecum, a small saclike evagination,then continues with the ascending colon, transverse colon, descendingcolon and the sigmoid (S-shaped) colon to the rectum. These body lumensmay suffer from pathologies, which can affect the anatomy orconfiguration of the lumen. For example, strictures, narrowing orclosure of a normally configured lumen can be caused by calcification orby the presence of scar tissue or a tumor. Strictures of the esophagusare a common complication of chronic gastroeosophagaeal reflux disease(GERD). Acute, complete obstruction of the esophagus may occur when foodis lodged in the esophageal stricture. Endoscopy is usually employed toretrieve the food and relieve the obstruction.

[0003] Several procedures are available for stretching (dilating) thestrictures without having to resort to surgery. These involve placing aballoon or a dilator across the stricture during an endoscopy procedure.

[0004] Methods for diagnosis of body lumens are usually symptom relatedor invasive. Non-invasive techniques of diagnosing the gastrointestinal(GI) tract include utilizing solid non-degradable swallowable autonomouselectronic or magnetically marked capsules. These autonomous capsulesinclude capsules for measuring motility in the GI tract, gastric pH(such as the Heidelberg capsule) and in vivo temperature (such as theCoreTemp™ capsule). Also, gastric transit may be measured by usingbiomagnetic measuring equipment such as a magnetically marked capsule,which is a solid non-degradable oral dosage form containing powderedmagnetite encapsulated in silicone rubber (W. Weitschies, R. Kotitz, D.Cordin, L. Trahms, (1997), J Pharm Sci, 86:1218-1222). Such capsules aretypically propelled through the GI system by peristalsis. Thesenon-invasive methods enable reaching parts of the intestine, especiallydistal parts of the small intestine (jejunum and ileum) that cannot bereached by other methods. However, in rare cases of severe strictures inthe GI tract, swallowing of a solid bolus (such as an electronic ormagnetically marked capsule) may cause obstruction of the GI tract.

[0005] Also, drug delivery devices that are solid non-degradable bolusesmay often be swallowed. Drug delivery devices may include diffusioncontrolled systems or environmentally responsive systems. In thesesystems there may be a combination of polymer matrices and bio activeagents (typically drugs) that allow for a drug to diffuse through thepores or macromolecular structure of the polymer upon introduction ofthe system in vivo. In some cases the devices are swelling-controlledrelease systems that are based on hydrogels. Hydrogels are polymers thatwill swell without dissolving when placed in water or other biologicalfluids. Thus, the swelling-controlled systems are initially dry and,when placed in the body, will absorb fluids and swell. The swellingincreases the polymer mesh size enabling the drug to diffuse through theswollen network into the external environment. These systems aretypically essentially stable in an in vivo environment and do not changetheir size either through swelling or degradation. The swallowing ofthese systems may thus, in cases of strictures in the GI tract, causeobstruction of the GI tract.

[0006] Non-invasive methods for detection of strictures, specifically inthe GI tract, usually include x-ray series that are based on intake ofx-ray opaque (radio-opaque) material (barium, gastrographine, orothers). The material resides for some time on the walls of the GItract, enabling examination of the x-ray images of the GI tract. Thistechnique has several drawbacks, namely, low detection rate and exposureto x-ray radiation.

[0007] In-vivo devices, pills, or other medical systems may need to passthrough the GI tract. However, it may be difficult to predict if suchdevices, pills, or systems may achieve safe passage through the GItract, short of actually attempting to pass the objects through thetract.

[0008] Therefore, there exists a need for an efficient and low-hazardmethod of examining a body lumen. Specifically, there exists a need fora safe and high performing method of detecting abnormalities in a bodylumen, such as abnormal motility in the GI tract, strictures or otherconfigurational abnormalities in body lumens. In addition, there existsa need to determine whether objects of a certain size and/or shape maypass safely through the GI tract.

SUMMARY OF THE INVENTION

[0009] Embodiments of the present invention provide a device and methodfor in vivo examination of a body lumen. In one embodiment of theinvention, a safe and simple non-invasive tester and method of testingof a body lumen's configuration are provided. Also provided according toan embodiment of the invention are a device and method for detectingconfigurational abnormalities in body lumens. Configurationalabnormalities may include clinical/anatomical abnormalities in bodylumens, such as strictures in the GI tract. According to anotherembodiment the invention provides a device and method for testingmotility in the GI tract.

[0010] A method, according to an embodiment of the invention, fortesting a body lumen may include the steps of a. introducing into thebody lumen a device, having initial dimensions for a predeterminedperiod and reduced dimensions after the predetermined period; and b.monitoring the device. The body lumen may be the GI tract and the devicemay be ingested. Typically the predetermined period is one hundred hoursor more, however, other periods may also be included according toembodiments of the invention.

[0011] According to one embodiment the device comprises a permeablecoating and a filling disposed within the coating. The filling iscapable of absorbing fluid from the body lumen. Typically, after thepredetermined period, the filling swells enough to burst the coating.

[0012] According to one embodiment the initial dimensions may be adiameter of about 11 mm and the reduced dimensions may be a diameter ofabout 2-10 μm. Other dimensions are possible.

[0013] A method according to an embodiment of the invention may includethe step of detecting a signal emanated from a monitoring device that isconnected to the device. The monitoring device, according to anembodiment of the invention, is typically of smaller dimensions than thedevice initial dimensions. The monitoring device may be a passivedevice, such as, an electronic ID tag, a magnetized device or anacoustic device. According to an embodiment of the invention a passivemonitoring device may be monitored by detecting a signal that isemanated from the monitoring device. Detecting an emanated signal may bedone, according to one embodiment, by generating an electromagneticfield to induce an induction power field having a first frequency andthen receiving a signal having a second frequency from the monitoringunit. The signal having a second frequency may be an electromagneticsignal or an acoustic signal. Other signals may be detected.

[0014] According to another embodiment the monitoring device activelyemits signals, such as electromagnetic or acoustic signals. According toyet a further embodiment the device includes a tag, such as radioactivematerial, magnetized particles or a radio opaque material. These tagsmay be detected by, for example, a radioactive emission detector, amagnometer or an x-ray machine. According to yet another embodiment thedevice includes a marker, such as a dye.

[0015] According to an embodiment of the invention a body lumen may betested by utilizing a device that comprises a dissolvable body, adissolvable plug affixed to the body, the body and plug defining aclosed receptacle, and an essentially impermeable outer coatingenclosing the plug and body. The coating typically covers less than theentire plug. The device according to an embodiment of the invention maycontain a tag, RFID, marker or any substance enclosed within the closedreceptacle. According to certain embodiments of the invention after thepredetermined period the body and plug are dissolved and the outercoating is depleted.

[0016] According to yet other embodiments the method may also includesensing at least one parameter of the body lumen, such as, pH, pressureand temperature. According to one embodiment data of the sensedparameter may be transmitted to an external receiving system.

[0017] According to an embodiment of the invention there is provided amethod for sensing a subject's GI tract. The method includes ingestingan in vivo sensing device which comprising a sensor, a transmitter fortransmitting sensed data and an electronic ID tag. According to oneembodiment the sensor may be an image sensor.

[0018] Also provided, according to an embodiment of the invention is amethod for controlled release of at least one substance in aconfigurationally or clinically abnormal GI tract. The method accordingto an embodiment of the invention includes ingesting a device, whichincludes a substance and comprises a dissolvable body, a dissolvableplug affixed to -the body, the body and plug defining a closedreceptacle, and an essentially impermeable outer coating enclosing theplug and body. The coating typically covers less than the entire plug.According to one embodiment, at least one substance may be dispersedwithin the plug and at least one substance may be enclosed in thereceptacle

[0019] According to a further embodiment of the invention there isprovided an in vivo imaging device comprising an image sensor, anillumination source, an internal power source and an electronic ID tag.The imaging device may also include a transmitter for transmitting imagedata to an external receiving system.

BRIEF DESCRIPTION OF THE FIGURES

[0020] The present invention will be understood and appreciated morefully from the following detailed description taken in conjunction withthe drawings in which:

[0021]FIG. 1A is a schematic illustration of the two phases of anexamining device in vivo, according to an embodiment of the invention;

[0022]FIG. 1B is a schematic illustration of the two phases of anexamining device in vivo, according to another embodiment of theinvention;

[0023]FIG. 2A is a schematic cross section illustration of an examiningdevice having a coating and a filling, in accordance with an embodimentof the invention;

[0024]FIG. 2B is a schematic side view illustration of an examiningdevice having a coating and a filling, in accordance with anotherembodiment of the invention;

[0025]FIG. 2C is a graph illustrating the step function followed by theexamining device according to an embodiment of the invention;

[0026]FIG. 3A is a schematic illustration of an examining devicecomprising a monitoring device in accordance with an embodiment of theinvention;

[0027]FIG. 3B is a schematic illustration of a monitoring systemaccording to an embodiment of the invention;

[0028]FIG. 3C is a schematic cross section illustration of a traceableexamining device in accordance with another embodiment of the invention;

[0029]FIG. 3D is a schematic illustration of a monitoring systemaccording to another embodiment of the invention; and

[0030]FIG. 4 is a schematic illustration of an examining deviceaccording to an embodiment of the invention.

DETAILED DESCRIPTION OF THE INVENTION

[0031] In the following description, various aspects of the presentinvention will be described. For purposes of explanation, specificconfigurations and details are set forth in order to provide a thoroughunderstanding of the present invention. However, it will also beapparent to one skilled in the art that the present invention may bepracticed without the specific details presented herein. Furthermore,well-known features may be omitted or simplified in order not to obscurethe present invention.

[0032] An atypical passage of an object through a body lumen or symptomsappearing after the insertion of an object into a body lumen may beindicative of an abnormal configuration of the body lumen. An examiningdevice according to embodiments of the invention, which can examine abody lumen and can be an indicator of the body lumen configuration, isdesigned to be safely exited from the body, independently of theconfiguration of the body lumen.

[0033] According to an embodiment of the invention a device comprises acoating and a filling. The coating has initial dimensions that arechangeable to final dimensions and the filling comprises particles thatare of final dimensions. Final dimensions enable passage of the devicein a body lumen configuration that is not enabled by the initialdimensions.

[0034] At a predetermined time a predetermined pressure, producedinternally in the device, is exerted on the coating. The predeterminedpressure causes the coating to rupture or collapse. Thus, at apredetermined time, the device is degraded or reduced, essentially in astep-wise manner, into dimensions that enable passage of the device in abody lumen configuration that is not enabled by the initial dimensions.

[0035] The predetermined pressure is typically unequal to the normallyprevailing endo-luminal pressure. The predetermined time is a periodgreater than the period it typically takes for the device to passthrough a normally configured body lumen.

[0036] The initial dimensions are typically determined in accordancewith the known anatomy and/or physiology of a body lumen. In its finalphase the dimensions of the examining device are typically smaller andits shape possibly changed such that it can freely pass through the bodylumen even if the lumen dimensions are smaller than expected inaccordance with the known anatomy and/or physiology of the body lumen.

[0037] Proceeding from an initial phase to a final phase of theexamining device, namely by producing a predetermined pressure withinthe device, may, for example, be promoted by endo-luminal conditions ormay be externally controlled. It should be appreciated that the devicetypically proceeds from an initial phase to a final phase, e.g. goingthrough a change in dimensions, when the predetermined pressure isexerted on the device coating. The predetermined pressure is typicallyproduced in the device and exerted on the device coating in vivo. It istherefore conceivable that a device according to an embodiment of theinvention will remain in its initial phase indefinitely. For example, ifthe device is not inserted in vivo or if the device is inserted in vivobut is exited from the body within a time period that is shorter thanthe predetermined time, the predetermined pressure will not be producedin the device and the device will not go through a change of dimensions.

[0038] The examining device may further comprise a monitoring mechanism,such as a radioactive, color or magnetic tag or an electronic ID tag(e.g., an RFID tag). Other monitoring mechanisms may be used. Anexternal operator, who can typically be advised of the phase the deviceis in at a given moment (as will be detailed below) may thus follow theprogression of the device through the body lumen. Additionally, thedevice may also comprise an examining mechanism, such as a thermometeror pH meter, for examining endo-luminal conditions, or other sensingdevices such as an imaging device.

[0039] In an embodiment of the invention the examining device is atesting device that comprises initial dimensions that will enable freepassage of the testing device through a normally configured body lumenbut not enable free passage of the testing device through certainstrictured or otherwise narrowed or abnormally configured body lumens.In its final phase the size of the testing device is typically smallerand its shape possibly changed such that it can freely pass through thebody lumen even if the lumen is abnormally configured.

[0040] In another embodiment of the invention the testing device may beused to simulate the passage of an in vivo device, such as a diagnosticand/or therapeutic device, through a body lumen. In this case, obtaininginformation on the passage of the testing device through the body lumencan be advantageous in designing a specific in vivo device or indetermining whether a certain in vivo device may be safely used on apatient. In one embodiment, different sized and shaped testing devicesaccording to an embodiment of the invention may be passed through a bodylumen to determine the most suitable size and shape for an in vivodevice to be freely and safely passed through this same lumen. Inanother embodiment the testing device comprises at least two phases, aninitial phase in which the testing device's dimensions approximatelyresemble the dimensions of a target in vivo device and a final phase inwhich the dimensions of the testing device are changed so as to enablethe testing device to pass through certain abnormally configured bodylumens. Passing of the testing device through a body lumen simulates thepassage of the target in vivo device through that body lumen and thus asafe method of indication is provided as to the transferability of thetarget in vivo device in the body lumen.

[0041] In the method according to an embodiment of the invention anexamining device can examine endo-luminal conditions, or test theconfiguration of a body lumen, detect configurational abnormalities in abody lumen and/or simulate the passage of an in vivo device in a bodylumen while posing no danger of long term obstruction of the body lumen.An examining device according to an embodiment of the invention in itsinitial phase comprises dimensions such that it can typically passthrough a body lumen and/or give a good approximation of the passage ofan in vivo device in the body lumen. In its final phase the examiningdevice's dimensions may be changed (typically reduced, although otherchanges are contemplated) so that it can pass through an abnormallyconfigured body lumen where the examining device in its initial phasecould not, because of its dimensions.

[0042] In case the body lumen is of unexpected dimensions (wherein theexpected dimensions are based, for example on the known or typicalanatomy and/or physiology of the body lumen) or in case of a strictureor any other configurational abnormality in the body lumen, theexamining device in its initial dimensions may be blocked fromcontinuing its typical or expected passage in the body lumen. After apredetermined time the examining device's dimensions may be changed suchthat the testing device, in its final phase, typically of degraded orreduced form, will not be blocked from passing even through a smaller orabnormally configured body lumen.

[0043] If no clinical or configurational abnormalities are present inthe body lumen the examining device's passage through the body lumenwill be typical and the examining device passes through the body lumenand exits the body while it is still in its initial dimensions. However,in a case in which the body lumen is abnormally configured (e.g., thereis a stricture) or if there is a clinical problem (e.g., slow or nomotility in the GI tract) the examining device is held back in the bodylumen and reaches its final dimensions while in the body lumen. Thedegraded or reduced device is able to continue its passage through thebody lumen to eventually exit the body. It will thus be appreciated thatthe device and method of the invention can be utilized to detectclinical and/or configurational abnormalities in body lumens throughwhich the device can be passed and exited, such as the GI tract, theurogenital tract, the reproductive tract, the oral-nasal cavity, etc, ora portion of any of these lumens.

[0044] A person skilled in the art can easily adjust the specific designof the examining device and the predetermined time period between aninitial and final phase of the examining device to be applicable to aspecific body lumen having specific and known anatomy and physiology.

[0045]FIGS. 1A and 1B are schematic illustrations of one embodiment ofthe invention. Referring to FIGS. 1A and 1B, an examining device 10,having initial dimensions, is inserted into a body lumen 100 and ismoved through the body lumen 100 (in the direction indicated by thearrow A) either actively or passively. The device 10, which has adiameter of, for example, 1-12 mm, can pass freely through the lumen 100that spans over a width of, for example, 1 mm to 10 cm, until astricture 101 is reached. At the stricture 101, there is only a residualfunctioning lumen of, for example, about 2-10 μm. The device (nowillustrated in a broken line and referred to by the numeral 10′) isunable to continue its passage through the body lumen 100 due to itsdimensions, which are larger than the dimensions of the body lumen atthe stricture 101. The device 10, in its initial dimensions, is thusblocked at the stricture 101.

[0046] After a predetermined time the device's 10 dimensions arechanged. The device 10 can be, for example, collapsed or disintegratedresulting in its final dimensions 12 (in Fig. 1A) or ruptured ordegraded, resulting in its final dimensions 14 (in FIG. 1B). In itsfinal dimensions 12 the device typically has reduced volume and aflattened shape, its diameter no more than, for example, 2-10 μm. In itsfinal dimensions 14 the device may be, for example, degraded intoseveral small sections or particles, each of which is no more than, forexample, 2 μm wide. The device in its final dimensions either 12 or 14can pass through the stricture 101 and can be existed from the body. Inalternate embodiments, the dimensions or shape of the body lumen 100 maybe different and the device 10 may be changed in other manners, to otherdimensions or shapes. For example, the device need -not be broken intomore than one section.

[0047] The examining device 10 can be, for example, capsule shaped,similar to the swallowable capsule described in U.S. Pat. No. 5,604,531to Iddan (which is hereby incorporated by reference) or similar in shapeand size to other pills, tables capsules and the like, known in the art.

[0048] In one embodiment, a capsule shaped testing device having initialdimensions of approximately 11 mm×26 mm can be used to test the GItract. The device is swallowed or otherwise placed in the GI tract (byan endoscope, for example) and is passively moved through the GI tractdue to peristalsis of the GI tract, until it is naturally excreted fromthe body. Alternatively, the device may be moved through the body lumenby an external operator by means such as an endoscope, needle, stentetc. Should the device be unable to move past a certain point, due tothe body lumen configuration at that point, the device will be left atthat point and will be degraded after a predetermined time. After thedevice is degraded or reduced, for example as shown in FIGS. 1A and 1 B,it will be naturally excreted from the body lumen.

[0049] Also, in one embodiment, a powerful magnet can be used from theoutside of the body to move a charged device within the body lumen.Should the external operator be unable to move the device past a certainpoint, due to the body lumen configuration at that point, the device canbe left at that point and it will be degraded after a predeterminedtime. After the device is degraded or reduced, for example as shown inFIGS. 1A and 1 B, it is able to passively and naturally exit the bodylumen.

[0050] In another embodiment the device 10 may be shaped or sized toresemble a target diagnostic or therapeutic device, which itself isdesired to be passed through the patient's body lumen, for example, aswallowable imaging device for purposes of imaging the GI tract. Thedevice 10 can be safely passed through the GI tract, to test thetransferability of such a device through the GI tract, while itsprogression can be monitored and/or the phase the device is in can bedetected (as will be further detailed below). In the event the devicecannot traverse a section of the lumen, its shape or dimensions maychange to allow passage.

[0051] Test devices according to several embodiments of the inventionare schematically illustrated in FIGS. 2A and 2B, however otherembodiments of devices having other shapes, dimensions and structuresmay also be used. According to one embodiment of the invention, a testdevice is made of an outer coating and internal filling. Test devicesfor the GI tract, for example, may initially have an outer coating andinternal filling each of, for example, a few μm to a few mm thick.Typically, the outer coating is a thinner layer than the internalfilling. According to some embodiments, the outer coating is designed toimpart mechanical strength to the device and keep the device shape anddimensions constant throughout the initial phase of the device. Thecoating also serves as a barrier between the internal filling and thesurrounding, such as, the endo-luminal environment. The coating istypically a layer or a plurality of layers of impermeable or slightlypermeable material or combination of materials, that is essentiallydurable (i.e., does not corrode or disintegrate) under in vivoconditions. The internal filling, which in one embodiment can be one ormore layers or a suspension or liquid or gas, typically constitutessmall particles or molecules and can produce pressure within the deviceby, for example, serving as an ion source or sink. The filling may alsocontain adhesives and fillers to, for example, further providemechanical stability to the device.

[0052] Referring to FIG. 2A, the test device 20 according to oneembodiment comprises an outer coating 24 and an internal filling 22. Theouter coating 24 is a layer of strong, slightly permeable material whichencapsulates the internal filling 22 and controls the diffusion rate ofsubstances from within the device and/or from the outside (e.g. the bodylumen environment) into the device. The internal filling 22 maintains anosmolarity that favors the inward or outward diffusion of ions, suchthat the internal filling will swell or be depleted (and exchanged forendo-luminal liquids) in a process which will preferably be determinedby the properties of the internal filling 22 and the rate of which willbe preferably limited by the properties of the outer coating 24.

[0053] In one embodiment the outer coating 24 may be made of a ParyleneC coated hydrogel polymer, such as ethyl cellulose acetate and theinternal filling 22 may be made of filler, preferably a biodegradablepolymer, such as polymer of lactide and golycollide (PLGA). In alternateembodiments, other materials may be used. Parylene C, which is a dimerof poly p-xylene with a substitution of a single chlorine molecule,provides a combination of properties such as a low permeability tomoisture, chemicals, and other corrosive gases. The hydrogel polymercreates a matrix that contains the filler and that is strong enough towithstand endo-luminal pressure. The filler absorbs liquid from the bodylumen environment which seeps through the hydrogel matrix at a ratewhich is typically determined by the osmotic gradient between theendo-luminal environment and the inner filling and by properties of theParylene C coating and of the hydrogel polymer, such as by the extent ofthe hydrogel polymer cross linking, its concentration, its thickness andso on.

[0054] The filler swells and after a period of time, starts pressingagainst the outer coating 24. The internal pressure rises as more liquidis absorbed. When the pressure reaches a certain, predetermined pointthe hydrogel matrix and the Parylene C coating rupture and the device 20is separate into smaller pieces and particles.

[0055] In another embodiment, the outer coating 24 may be a lowsolubility material that is permissive to an inward flow of endo-luminalliquids or a soluble material that is initially impermeable toendo-luminal liquids but becomes permeable as it is dissolved, due tothinning of the layer. The inward flow of endo-luminal liquids causesthe pressure in the device 20 to be elevated and ultimately the outercoating 24 is ruptured, thereby diminishing the dimensions of the device20.

[0056] For example, in a device having a diameter of 11 mm, a layer ofParylene C, a few μm thick (5-20 μm) can be used as the outer coating 24and a 11 mm thick filling of any suitable filler can be used as theinternal filling 22. The thickness of the outer coating layer serves toregulate the rate of the inward flow of endo-luminal liquids. In anotherembodiment the outer coating 24 can be made of a 10 μm thick layer ofParylene C and a 0.5 mm thick layer of gelatin. The gelatin, which maybe soft, hard or vegetable gelatin, may be cross-linked to increase itsdurability. Thus, a device comprising an outer layer made of Parylene Cmay be designed to go through a change in dimensions at a desired rate.Of course, other dimensions, and other suitable substances, may be used.

[0057] The device 20 can be manufactured to be of a shape that issimilar to pharmaceutical tablets, pills, capsules etc, by molding,pressing, extruding and so on. For example, the internal filling 22,which may include microspheres of a hydrophilic substance encapsulatedwithin a fatty based matrix or within a coating of Parylene C, may bepressed into a tablet about 11 mm thick, and then coated by a thin(about 10 μm), outer coating 24 that, typically, is not degradable underendo-luminal conditions (such as low pH, temperature, enzymaticdegradation etc.). When in use, the microshperes absorb liquids from theenvironment and swell, building up pressure ultimately causing the outercoating 24 to rupture.

[0058] In an alternative embodiment the osmolarity of the internalfilling may favor a diffusion of ions into the body lumen, a gradualdepletion of the internal core and a flow of liquids into the device.The depleting internal core is exchanged for liquids, which exertpressure on the device coating, and after a predetermined point theouter coating is ruptured and the entire device is diminished.

[0059] It should be appreciated that the device may comprise more thantwo layers, each layer having its own dynamics, as described above.Further, it should be appreciated that the change in dimension of thedevice can be influenced by different parameters, such as by thethickness of each layer or by different properties of the materialfabricating each layer etc. A predetermined pressure that is suitablefor rupturing one coating may be unsuitable for rupturing anothercoating. For example, different hydrogel fillings can be induced to gothrough a change of swelling. A thermo-responsive hydrogel can bestimulated by a change in temperature to go through polymer-polymer andwater-polymer interactions, which results in a change in swelling of thehydrogel. Likewise, an acidic or basic hydrogel will be induced by achange in pH. The swelling of modified hydrogels can also be stimulated.For example, a hydrogel containing electron accepting groups will bestimulated by the presence of electron donating compounds, a polyelectrolyte hydrogel will be stimulated in the presence of an appliedelectric field and magnetic particles dispersed in microspheres, such asalginate microspheres, will be stimulated in the presence of an appliedmagnetic field. Thus, a device according to an embodiment of theinvention may be externally controlled, namely, the transition of thedevice from an initial phase to a final phase can be controlled, forexample, by artificially changing the endo-luminal temperature or pH orby externally applying an electric or magnetic field to the body lumen.

[0060] External control of the transition of the device from an initialphase to a final phase may be useful in cases in which the device isblocked in a body lumen having an environment that does not favor thetransition from an initial phase to a final phase. For example, thedevice may be blocked in a patient's large intestine due to a stricturein the large intestine. The endo-luminal environment in the largeintestine might, at times, not be diluted enough to provide thepredetermined pressure by an inward flow of endo-luminal liquids. Thetransition of the device to its final dimensions may then be initiatedexternally, for example, as described above, in order to contribute tothe diminishing of the device.

[0061] It should be appreciated that the device according to anembodiment of the invention can be made of materials that are degradableby external methods such as by ultrasound, in case an external operatorwishes to diminish the device before that device is changed to its finaldimensions.

[0062] In FIG. 2B the device 200 comprises an outer coating 204 and aninner filler (not shown). The outer coating 204 is differentiallystrengthened, i.e., having areas of different strengths. Device 200 canbe, for example, capsule shaped or otherwise shaped. The outer coating204 and inner filler can be made of any suitable material, for example,as discussed above. Specific areas in the outer coating 204 are weakerthan neighboring areas such that when pressure is exerted on theseweaker areas, the outer coating 204 breaks or collapses in the vicinityof these areas. In the example illustrated in FIG. 2B, a patch 212 atone end of the device 200 or a band 214 around the middle of the device200 are weaker than neighboring areas 212′ and 214′. For example, patch212 and/or band 214 may be thinner than neighboring areas and will thusare more susceptible to pressure than the neighboring areas 212′ and214′. Alternatively, patch 212 and/or band 214 can be more permeable toliquids than neighboring areas and thus, while in a body lumen, a largerflow of endo-luminal liquids pass through these areas than throughneighboring areas. This differential flow of liquids causes pressure tobe exerted in the vicinity of the more permeable areas, thereby causingthe outer coating 204 to break or collapse in these areas. Differentialpermeability in these areas can be caused by, for example, using athinner layer of coating in these areas, by puncturing holes 213 inthese areas, by using different materials to manufacture the differentareas and so on.

[0063] A device 200 can include an outer coating 204 and an internalfiller that is a body of gas or liquid. Alternatively, the device mayinclude multiple layers; outer coating layers and internal fillerlayers, as described above. Pressure of a certain amount exerted by thein or out flow of liquids or by swelling of an internal core layeragainst the outer coating causes the outer coating 204 to break atspecific weakened areas, such as at patch 212 and/or along band 214.Thus, device 200 having an outer coating 204 with areas of differentialstrength can be designed to go through a change of dimensions in astep-wise manner, wherein the breaking of the outer coating, which canbe brought about gradually, will cause an immediate change of dimensionsof device 200.

[0064] In such an embodiment, during the initial phase, while thepressure in the device is increasing, the outer coating is unaffected bythe rising pressure or by endo-luminal conditions (even if there iserosion of the outer coating during the initial phase, it will typicallybe not more than about 5% of the initial outer coating dimensions) andthus, the device shape and dimensions are not significantly changed.However, once the predetermined pressure is achieved the outer coatingwill collapse or rupture and the device's dimensions will be reduced ina step-wise or an approximation of a step-wise manner. Thus, althoughboth outer coating and internal filling may change dimensions ordissolve gradually, the overall reaction is an approximation of a stepfunction.

[0065] An approximation of a step-wise reaction, according to anembodiment of the invention, is schematically presented in FIG. 2C. Thegraph shown in FIG. 2C, which represents the dissolving of a two-layerdevice according to one embodiment, includes two exponents representedas (a) and (b). The first exponent (a) represents an outer layer withessentially fixed dimensions (e.g. a change of dimensions up to about 5%of the initial dimensions) while the second exponent (b) represents adepleting or dissolving inner layer. The outer layer protects andprevents dissolving or depleting of the inner layer. However, once theouter layer is dissolved or ruptured the process of dissolving ordepleting of the inner layer is initiated. The combination of the twoexponents approximates the required step function.

[0066] A testing device is not always easily seen when it is in aperson's body and it might not be known when the device exits the body,for example in the case of a testing device for the GI tract. A personhaving swallowed or otherwise ingested a test capsule does not alwaysknow when and in what dimensions the test capsule exited his body. Inone embodiment, a test capsule for the GI tract is designed to stay inits initial dimensions, under in vivo conditions, for about 100 hours ormore. In alternate embodiments, other time limits may be used, andtesting devices for other body lumens may be designed in accordance withthe specific body lumen having specific and known anatomy andphysiology.

[0067] In another embodiment of the invention a monitoring mechanism isincluded, which enables a user to externally follow the progress of thetesting device or otherwise track the testing device in the body lumen.Slowing down or blocking of the device in the body lumen, for a periodthat is longer than the time it typically takes for a device to passthrough a normally configured lumen, implies an abnormality of the bodylumen. The location of the testing device at a given moment in a bodylumen can be determined by known methods. Thus, clinical abnormalitiesand/or conformational abnormalities, such as strictures in the GI tract,can be identified and localized to specific areas in the body lumen.

[0068] Testing devices according to some embodiment of the invention areillustrated and exemplified in FIGS. 3A-3D. Referring to FIGS. 3A and 3Bthe testing device 40, which may be designed and fabricated as discussedabove, includes, for example, a thin semi permeable rate limitingcoating 401, such as a 10 μm thick Parylene C coating, a thicker,mechanical stability imparting shell 405, such as a 1-2 mm thick layerof gelatin, a swellable filler 407, such as a 3-4 mm thick layer of ahydrogel and a monitoring device 43, which in one embodiment isapproximately 3 mm wide. The device 40 is swallowed or otherwiseinserted into the patient's 300 GI tract and the patient 300 is thenmonitored by being placed in the vicinity of a receiving system 305, aswill be further detailed below.

[0069] The monitoring device 43 may be, for example, a passive ID tag,advising of its presence only upon external activation. Such an ID tagmay be of known construction including, for example, a processor (notshown), a transmitter (not shown) and an antenna (not shown) to receiveenergy from an external transmitting device 303. Such miniature passiveID tags are used for example as implantable tags for animalidentification. Such implantable tags are manufactured by Tiris,Microchip, and other companies.

[0070] In alternate embodiments, the tag may include other components;for example, the tag may include a Gunn diode instead of a processor. Inanother embodiment the tag may include a passive acoustic element thatwill respond to external induction by creating at least one acousticsignal, such as a squeak, beep or click. An external operator can inducethe tag to send an acoustic signal and can then listen for the signal byputting a stethoscope, for example, to the patient's body. Hearing thesignal will indicate that the tag is still in the patient's body. Theoperation of the tag can be coupled to the device such that if thedevice has disintegrated the tag will not respond by sending an acousticsignal. For example, a component of the tag, such as a battery forpowering the tag, may be attached to the device shell such that when thedevice shell is ruptured or collapsed the battery will no longer beconnected to the tag and the tag will not be able to produce an acousticsignal.

[0071] In another embodiment the monitoring device 43 is magnetized toobtain a net magnetic dipole moment. After the device 40 is introducedin vivo, its magnetic field distribution over the body lumen can berecorded for several time intervals with a receiving system 305 (e.g., amagnetometer) and at each time point the position of the device withinthe body lumen may be calculated from the measured field distribution,assuming a magnetic dipole model.

[0072] Optionally, the monitoring device 43 may be active, such as abeacon continuously or periodically signaling to an external receivingsystem 305, advising its presence. In one embodiment, the monitoringdevice 43 is an acoustic beacon. The acoustic beacon, according to anembodiment of the invention, generates at least one acoustic signal.According to another embodiment the acoustic beacon includes anelectronic circuit that produces a periodic pulse (for example every15-30 seconds). The circuit is connected to an acoustic element, such asa buzzer, clicker, beeper etc., for example via an electro-acousticconverter, so that an acoustic signal is periodically generated.

[0073] In one embodiment the monitoring device 43 is powered by a PowerPaper™ power source provided by Power Paper Ltd., Israel.. Preferably,the battery can last for over 200 hours. The monitoring device 43 may beoperated by a read-relay switch. The switch can be turned to an ON orOFF position by distancing an external magnet from the monitoring device43, as known in the art. Thus, for example, the device 40, whichincludes a monitoring device 43, such as an acoustic beacon, can bepackaged in a magnetic package. The acoustic beacon is turned off whilestill in the magnetic packaging. Once the device 40 is released from thepackaging, typically just prior to inserting the device 40 in vivo, themonitoring device 43 is activated. In another embodiment the acousticbeacon can be activated only after device 40 has ruptured ordisintegrated.

[0074] An external operator can, at any point after the device 40 hasbeen inserted in vivo, listen for the acoustic signal by any knownmeans, for example, by putting a stethoscope to the patient's body.Hearing the signal indicates that the tag is still in the patient'sbody. The approximate location of the monitoring device may be inferred.In an alternative embodiment, signals from the monitoring device 43 arereceived by receiving system 305 and the location of the monitoringdevice 43 can be calculated by known triangulation methods. Thecalculations, according to an embodiment of the invention, are carriedout on a processing unit 408. Thus, the monitoring device 43 can bemonitored and its position can be known, while it is in the patient's300 body and when it exits the patient's body.

[0075] The monitoring device 43, typically a miniature device, is shapedand sized such that it in itself can freely pass through a body lumeneven if the body lumen is strictured or narrowed or otherwise abnormallyconfigured. In such a case, the device 40 is ruptured or collapsed orotherwise altered as described above and the diminished device 40 andthe monitoring device 43 pass freely through the body lumen to exit thepatient's body.

[0076] Referring to FIGS. 3C and 3D, a testing device 400 in oneembodiment comprises an outer coating 404 and an internal filling 402.The outer coating 404 and internal filling 402 can be fabricated asdescribed above. The internal filling 402, which may be a filler, mayfurther comprise a marker 403. In one embodiment the marker is radioopaque material, such as barium sulfate, or other detectable material,such that the testing device 400 can be viewed by x-ray or otherdetection methods. In an alternative embodiment the marker is a dye,which can be dispersed or embedded in the filling. In yet anotherembodiment the marker is magnetite (Fe₃O₄), for example, powderedmagnetite in poly(methyl methacrylate). In this case the device 400 ismagnetized to obtain a net magnetic dipole moment such that the device400 can be monitored as described in reference to FIGS. 3A and 3B.Further, in yet another embodiment the marker is a radioactive marker.In another embodiment the marker may be a chemical that can interactwith the patient's body to achieve a sensation that is felt by thepatient. For example, niacin that is let to interact with the patient'sbody may cause sensation, advising the patient that the niacin has beenreleased into his body.

[0077] The device 400 is inserted into a patient's 300 GI tract and canbe monitored by a suitable detector 301, for example, an x-ray machine,a gamma camera or a magnetometer. The detector 301 is typically movedalong the patient's 300 body and utilizing a plurality of detectors orreceivers (not shown) and a processing unit 302, can detect andcalculate, by known methods, the location of the marker 403.

[0078] Typically, when the device 400 reaches its final dimensions theouter coating 404 is dissolved or ruptured and the internal filling 402and any marker 403 dispersed or embedded therein, is released into thebody lumen. Thus, according to one embodiment a patient 300 or anexternal operator can be advised of the fact that the device 400 hasreached its final dimensions by a sudden sensation, for example or bythe appearance of a marker in body lumen contents or excretions, forexample by the appearance of colored stool, etc. In another embodimentof the invention a marker 403 can be used to mark the location of astricture or other configurational abnormality. The marker 403, whichmay be a dye, can be dispersed or embedded within the internal fillingor contained in a separate layer under the coating 404, to be exposedwhen the outer coating 404 is dissolved or ruptured. Thus, a marker canbe let out in a lumen at the location of an abnormal configuration ofthat lumen (such as at the location of a stricture) and can consequentlymark the location. In one embodiment a subject may swallow a deviceaccording to an embodiment of the invention, for testing the GI tract.In case of a stricture the device will be delayed at the stricture andeventually it will go through a change of dimensions, as describedabove, releasing a marker at the site of the stricture. A surgeon willthen be able to identify the location of the stricture by externallyviewing the GI tract and detecting the marker. The procedure of removinga stricture, for example, in the GI tract may thereby be facilitated. Inanother embodiment the device may also include a tag, such as the tagsdescribed above, for assisting in localizing the device.

[0079] In some embodiments it may be preferable that the marker be longlasting (for example, a few days) and visible through lumen tissues, sothat it is detectable from the outside of the lumen. Examples of suchmarkers can be Indian ink or known metal markers. Also, particularly foruse in the GI tract, edible markers, such as food coloring, may beemployed.

[0080] In an additional embodiment the marker may be sprayed out of thedevice, for example by producing high pressure in the layer thatcontains the marker, such that when this layer is exposed its contentsare forcefully propelled from the device onto the nearby lumen tissue.Other methods of forcefully propelling the marker from the device may bepossible, such as by employing an injecting mechanism in the device thatis activated when the outer coating is dissolved or ruptured.

[0081] According to another embodiment, as long as the outer coating 404is intact and the marker 403 is enclosed within the outer coating 404the marker 403 will be detectable by the detector 301. If the outercoating 404 is dissolved or ruptured the internal filling 402 and anymarker 403 dispersed or embedded therein will be released into the bodylumen and dispersed such that the marker 403 will no longer bedetectable by the detector 301. Thus, the testing device 400 can bemonitored while in its initial dimensions, by using detector 301. Oncethe device 400 reaches its final dimensions the marker 403 will bedispersed and undetectable by detector 301. The device 400 may thus bemonitored and its position, while in the initial phase, can becalculated. In the final phase the filling will be dispersed in the bodylumen environment such that the signal typical of the initial phase willno longer exist. Device 400 may also contain a monitoring device, suchas the monitoring device 43 (FIG. 3A) for further monitoring after thedevice 400 reaches its final dimensions.

[0082] Additionally, monitoring device 43 may also serve as a platformfor additional in vivo sensing units, such as a pH meter, a thermometer,an imager, a pressure detector etc. The sensing units may transmit data,wirelessly or not, to an external receiving system while traversing thebody lumen. Optionally, the devices according to embodiments of theinvention may comprise a miniature in vivo sensing unit, as above, thatis not connected to the monitoring device 43.

[0083] According to one embodiment an in vivo imaging device, such asthe device described in WO 01/65995 (incorporated herein by reference)may include an electronic tag, such as an RFID. An imaging device,according to one embodiment may include an electronic tag, an imagesensor, an illumination source and an internal power supply, such as abattery. The imaging device may also include a transmitter fortransmitting image data to an external receiving system.

[0084] Reference is now made to FIG. 4, which schematically illustratesan examining device according to one embodiment of the invention. Device50 has a body 58 and a plug 58′, which are typically but not necessarilymade of different materials. The body 58 and plug 58′ enclose an innerspace which typically contains a filler 52 and an ID tag 53. The body 58and plug 58′ are coated by a thin coating layer 54, except at window 56.At window 56 the plug 58′ may be exposed and come in direct contact witha body lumen environment. According to one embodiment, the device 50 canbe assembled by affixing (for example by gluing) a filler and ID tagfilled body to a plug having a protrusion 56′. The filler 52 filled body58 with the protrusion 56′ containing plug 58′, fixed to it are thencoated by coating layer 54. The protrusion 56′ is then cut off close tothe plug 58′, leaving a window 56 that is not coated by coating layer54.

[0085] Device 50 can be inserted into the GI tract and may be propelledthrough GI tract by, for example, peristalsis, as described above. Thecoating layer 54 is typically impermeable to GI tract liquids while theplug 58′ is typically permeable to the GI tract liquids. Liquids fromthe environment may thus enter through window 56, which is unprotectedby coating layer 54. GI tract liquids will diffuse or flow in throughwindow 56, dissolving the plug 58′, at a rate that can be dependant onparameters, such as, the size of window 56, the properties of thematerial fabricating plug 58′ and the thickness of the plug 58′. After apredetermined time the plug 58′ will dissolve enough to create anopening through window 56 through which GI tract liquids may come intocontact with the body 58 and through which filler 52 and eventually, IDtag 53 may leave device 50. The body 58 is typically made of a materialthat is faster to dissolve than the material fabricating the plug 58′.Thus, once an opening is created in plug 58′ the device 50 will berapidly depleted of its contents leaving only an empty coating layer 54.

[0086] A device according to an embodiment of the invention may be madeof, for example, a gelatin body and a wax plug. Other materials may beused. The device may be filled with powdered sugar into which a glasscoated 12×2 mm RF ID tag (or other suitable identification or beacondevice) is inserted. The filled body and plug may be coated by, forexample, an 8-10 μm layer of Parylene C. In alternate embodiments theplug may be made of, for example, lipophilic material of plant origin orhydrocarbons (simple and/or complex). According to an embodiment of theinvention the plug may be made of essentially hydrophobic material,e.g., wax. According to one embodiment the hydrophobic material maycomprise micro-particles to facilitate flow of body fluids into the plugand to facilitate the disintegration of the plug. A system that may besuitable to use in an embodiment of the present invention may be asystem of nano-particles, for example, formed of a solid hydrophobicinner core and a cationic exterior. The nano-particles may beencapsulated in micro-capsules. In one embodiment the nano-particles maybe encapsulated in moisture sensitive micro-capsules. Such systems areproduced, for example, by Salvona, USA. The device may be filled with,for example, powdered sugar and other exepients. Barium or othersuitable material may be mixed into the filling for easily monitoringthe device by x-ray. Alternatively, the device may not need a filling,which is usually intended to impart mechanical strength to the device.For example, the gelatin body may be thick enough to impart the requiredmechanical strength without being filled with a powder filling. Thedevice containing the ID tag may be monitored by using a reader such asa suitable reader provided by Trovan Ltd. UK. The tag may be the tagsdescribed herein, such as a radioactive marker, a magnetic device, or aradio based tag.

[0087] In an alternative embodiment, a device, according to anembodiment of the invention may be utilized for controlled release ofsubstances into a body lumen, such as the GI tract. According to anembodiment of the invention substances, such as an active agent, amedicament or markers may be included in a component or compartment ofthe device, to be released in a body lumen. In one embodiment thesubstances may be released at a specific site, typically at a site of anabnormal configuration, such as a stricture. According to one embodimentthe filler 52 may include medicaments specifically intended to treat astrictured or constipated GI tract. Such medicaments may include, forexample, steroids. For example, one or more active agents in powder formmay be mixed with any suitable filler, for example, as described above.According to another embodiment one or more active agents may beincluded in a nano-particle that is microencapsulated in plug 58′. Inyet another embodiment one or more active agents may be incorporated inbody 58. The active agents may be soluble in the components of the plug58′ or the body 58 or the active agents may be dispersed in a solidmatrix, for example, in material comprising body 58 or in thenano-particles that are included in the plug 58′. Similarly, a marker,as discussed above, may be incorporated into components of a deviceaccording to an embodiment of the invention. Medicaments or othersubstances may be inserted into the device in form of a tablet, gel orliquid. According to one embodiment a liquid solution containing asubstance may be an oily solution that does not dissolve the gelatinbody. The incorporation of substances, such as active agents or markers,into components of the device, according to embodiments of theinvention, may be accomplished by any suitable method known in the art,for example, as known in the pharmaceutical field.

[0088] A device according to an embodiment of the invention is typicallydisintegrated and its contents released after a predetermined period,for example after 100 hours or more. Further, a device according to anembodiment of the invention is stopped in a clinically orconfigurationally abnormal lumen and is disintegrated and its contentsreleased substantially only in a clinically or configurationallyabnormal lumen, for example, at the site of a stricture or in aconstipated GI tract. Thus, medicaments or markers that are intended tospecifically treat or mark strictures or other configurationalabnormalities in a body lumen or active agents specifically meant totreat motility abnormalities, such as constipation, can be released,according to embodiments of the invention, in a site specific manner forspecific treatment of the abnormality.

[0089] According to one embodiment a suspected strictured GI tract maybe tested by ingesting a device according to an embodiment of theinvention. According to one embodiment the device disintegrates after aperiod of 12 or 24 hours. A patient suffering from an acutely stricturedintestine may show symptoms 12 or 24 hours after ingesting the devicebolus. In this case the patient is typically operated on immediately.The device according to an embodiment of the invention may comprise amarker such that a strictured site is marked shortly prior to thesurgical procedure, directing the surgeon immediately to the site. Inyet another embodiment the device may comprise a medicament such thatstricture site may receive medical treatment just prior to the surgicalprocedure.

[0090] It will be appreciated by persons skilled in the art that thepresent invention is not limited by what has been particularly shown anddescribed herein above. Rather the scope of the invention is defined bythe claims, which follow:

What is claimed is:
 1. A method for testing a body lumen, the methodcomprising the steps of: introducing into the body lumen a device, saiddevice having initial dimensions for a predetermined period and reduceddimensions after the predetermined period; and monitoring the device. 2.The method according to claim 1 wherein the body lumen is the GI tract.3. The method according to claim 2 wherein the step of introducing thedevice comprises ingesting the device.
 4. The method according to claim1 wherein the predetermined period is a period of approximately onehundred hours or more.
 5. The method according to claim 1 wherein thedevice comprises a permeable coating and a filling disposed within saidcoating, the filling being capable of absorbing fluid from the bodylumen.
 6. The method according to claim 5 wherein, after thepredetermined period, the filling swells enough to burst the coating. 7.The method according to claim 1 wherein, after the predetermined period,the coating is burst.
 8. The method according to claim 1 wherein thecoating comprises at least one layer.
 9. The method according to claim 1wherein the coating includes a material or combination of materialsselected from the group consisting of: parylene C, hard gelatin, softgelatin, vegetable gelatin and a hydrogel.
 10. The method according toclaim 9 wherein the hydrogel is ethyl cellulose acetate.
 11. The methodaccording to claim 1 wherein the filling comprises at least one layer.12. The method according to claim 1 wherein the filling includes amaterial or combination of materials selected from the group consistingof: a filler, a biodegradable polymer, microparticles of a hydrophilicsubstance and a hydrogel.
 13. The method according to claim 12 whereinthe biodegradable polymer is a- polymer of lactide and glycollide. 14.The method according to claim 12 wherein the filling further comprisesadhesives.
 15. The method according to claim 1 wherein the coating isthinner than the filling.
 16. The method according to claim 1 whereinthe initial dimensions comprise a diameter of approximately 1-12 mm andwherein the reduced dimensions comprise a diameter of approximately 2-10μm.
 17. The method according to claim 1 wherein the step of monitoringthe device comprises detecting a signal emanated from a monitoringdevice, said device including at least the monitoring device.
 18. Themethod according to claim 17 wherein the monitoring device is of smallerdimensions than the device initial dimensions.
 19. The method accordingto claim 17 wherein the monitoring device is a passive device.
 20. Themethod according to claim 19 wherein the monitoring device is selectedfrom the group consisting of: an electronic ID tag, a magnetized deviceor an acoustic device.
 21. The method according to claim 19 wherein thestep of detecting a signal emanated from a monitoring device comprisesthe steps of: inducing the monitoring device to emanate a signal; anddetecting the emanated signal.
 22. The method according to claim 21wherein the step of inducing the monitoring device comprises generatingan electromagnetic field to induce an induction power field having afirst frequency and wherein the step of detecting the emanated signalcomprises receiving a signal having a second frequency from themonitoring unit.
 23. The method according to claim 22 wherein the signalhaving a second frequency is an electromagnetic signal or an acousticsignal.
 24. The method according to claim 17 wherein the monitoringdevice actively emits signals.
 25. The method according to claim 24wherein the signals are electromagnetic or acoustic signals.
 26. Themethod according to claim 1 further comprising the step of sensing atleast one parameter of the body lumen.
 27. The method according to claim26 further comprising the step of transmitting data of the sensedparameter.
 28. The method according to claim 26 wherein the sensedparameters are selected from the group consisting of: pH, pressure andtemperature.
 29. The method according to claim 1 wherein the step ofmonitoring the device comprises detecting a tag contained in the device.30. The method according to claim 29 wherein the tag is selected fromthe group consisting of: radioactive material, magnetized particles or aradio opaque material.
 31. The method according to claim 30 wherein thestep of detecting the tag comprises using a radioactive emissiondetector, a magnometer or an x-ray machine.
 32. The method according toclaim 1 wherein the step of monitoring the device comprises releasing amarker from the device; and detecting the marker.
 33. The methodaccording to claim 32 wherein the marker is a dye.
 34. The methodaccording to claim 1 wherein the device comprises a dissolvable body; adissolvable plug affixed to the body, said body and plug defining aclosed receptacle; an essentially impermeable outer coating enclosingthe plug and body, said coating covering less than the entire plug. 35.The method according to claim 34 wherein the device further comprises atag enclosed within the closed receptacle.
 36. The method according toclaim 34 wherein the body includes gelatin.
 37. The method according toclaim 34 wherein the plug includes a material selected from the groupconsisting of: wax, lipophilic material of plant origin or hydrocarbons.38. The method according to claim 34 wherein the outer coating includesparylene C.
 39. The method according to claim 34 wherein the devicefurther comprises a filler.
 40. The method according to claim 34 whereinafter the predetermined period the body and plug are dissolved and theouter coating is depleted.
 41. The method according to claim 34 whereinthe device further comprises an RFID tag.
 42. A method for sensing asubject's GI tract the method comprising the step of: ingesting an invivo sensing device, said device comprising a sensor, a transmitter fortransmitting sensed data and an electronic ID tag.
 43. The methodaccording to claim 42 wherein the sensor is an image sensor.
 44. Themethod according to claim 42 wherein the electronic ID tag is an RFID.45. The method according to claim 42 wherein the device furthercomprises an internal power source.
 46. A method for controlled releaseof at least one substance in a configurationally or clinically abnormalGI tract, the method comprising the step of: ingesting a device, saiddevice including the substance and the device comprising a dissolvablebody; a dissolvable plug affixed to the body, said body and plugdefining a closed receptacle; and an essentially impermeable outercoating enclosing the plug and body, said coating covering less than theentire plug.
 47. The method according to claim 46 wherein the substanceis an active agent or a marker.
 48. An in vivo imaging device comprisingan image sensor, an illumination source, an internal power source and anelectronic ID tag.
 49. The imaging device according to claim 48 furthercomprising a transmitter for transmitting image data to an externalreceiving system.
 50. An in vivo device for controlled release of atleast one substance in a configurationally or clinically abnormal GItract, the device comprising the substance; a dissolvable body; adissolvable plug affixed to the body, said body and plug defining aclosed receptacle; and an essentially impermeable outer coatingenclosing the plug and body, said coating covering less than the entireplug.
 51. The in vivo device according to claim 50 wherein the substanceis enclosed in the receptacle.
 52. The device according to claim 50wherein at least a first substance is dispersed within the plug and atleast a second substance is enclosed in the receptacle.
 53. The deviceaccording to claim 50 wherein the substance is an active agent or amarker.
 54. The device according to claim 50 further comprising anelectronic ID tag.